The capsular saccharides of bacteria have been used for many years in vaccines against capsulated bacteria. As saccharides are T-independent antigens, however, they are poorly immunogenic. Conjugation to a carrier can convert T-independent antigens into T-dependent antigens, thereby enhancing memory responses and allowing protective immunity to develop. The most effective saccharide vaccines are therefore based on glycoconjugates, and the prototype conjugate vaccine was against Haemophilus influenzae type b (‘Hib’) [e.g. see chapter 14 of ref. 97].
Another bacterium for which conjugate vaccines have been described is Staphylococcus aureus (S. aureus). Various polysaccharides have been isolated from S. aureus for use in glycoconjugates. Two polysaccharides of particular interest are the type 5 and type 8 capsular polysaccharides. Approximately 60% of human S. aureus strains are type 8 and approximately 30% are type 5. Much of the work on type 5 and type 8 conjugates has been performed by Fattom et al., and is described in documents such as references 1 to 9. The Fattom process for type 5 and type 8 polysaccharide conjugation typically involves thiolation of a purified polysaccharide using cystamine. The reaction relies on the presence of carboxylate groups in the capsular polysaccharide. These groups react with cystamine in the presence of a carbodiimide, e.g. EDAC. The derivatised polysaccharide is then conjugated to a carrier protein such as the Pseudomononas aeruginosa endotoxin A (ETA), typically via a linker [2]. Other researchers have carried out conjugation of purified type 5 and type 8 capsular polysaccharides by reductive amination [10 and 11]; glutaradehyde coupling [10]; or reaction of hydroxyl groups on the polysaccharides with cyanylating agents like CDAP [12] or cyanuric trichloride [13].
Although conjugate vaccines prepared by the Fattom process have been shown to be safe and immunogenic in humans [5], there remains a need for further and better ways of preparing conjugates of S. aureus type 5 or type 8 capsular polysaccharides.